Acid-base disturbances in nephrotic syndrome: analysis using the CO2/HCO3 method (traditional Boston model) and the physicochemical method (Stewart model)

Abstract

Background: The Stewart model for analyzing acid-base disturbances emphasizes serum albumin levels, which are ignored in the traditional Boston model. We compared data derived using the Stewart model to those using the Boston model in patients with nephrotic syndrome.

Methods: Twenty-nine patients with nephrotic syndrome and six patients without urinary protein or acid-base disturbances provided blood and urine samples for analysis that included routine biochemical and arterial blood gas tests, plasma renin activity, and aldosterone. The total concentration of non-volatile weak acids (A_TOT), apparent strong ion difference (SIDa), effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated according to the formulas of Agrafiotis in the Stewart model.

Results: According to the Boston model, 25 of 29 patients (90%) had alkalemia. Eighteen patients had respiratory alkalosis, 11 had metabolic alkalosis, and 4 had both conditions. Only three patients had hyperreninemic hyperaldosteronism. The Stewart model demonstrated respiratory alkalosis based on decreased PaCO₂, metabolic alkalosis based on decreased A_TOT, and metabolic acidosis based on decreased SIDa. We could diagnose metabolic alkalosis or acidosis with a normal anion gap after comparing delta A_TOT [(14.09 - measured A_TOT) or (11.77 - 2.64 × Alb (g/dL))] and delta SIDa [(42.7 - measured SIDa) or (42.7 - (Na + K - Cl)]). We could also identify metabolic acidosis with an increased anion gap using SIG > 7.0 (SIG = 0.9463 × corrected anion gap-8.1956).

Conclusions: Patients with nephrotic syndrome had primary respiratory alkalosis, decreased A_TOT due to hypoalbuminemia (power to metabolic alkalosis), and decreased levels of SIDa (power to metabolic acidosis). We could detect metabolic acidosis with an increased anion gap by calculating SIG. The Stewart model in combination with the Boston model facilitates the analysis of complex acid-base disturbances in nephrotic syndrome.

Keywords: Acid–base disturbance; Metabolic acidosis; Nephrotic syndrome; Renin–angiotensin–aldosterone system; Respiratory alkalosis.

Fig. 1

Determination of pH in the Stewart model. In the Stewart model, PaCO₂, A_TOT, and SIGc have powers toward acidosis. On the other hand, SIDa has a power toward alkalosis. In healthy individuals, pH should be 7.40. In nephrotic syndrome, patients are alkalotic due to decreased levels of PaCO₂, decreased A_TOT due to hypoalbuminemia, and decreased SIDa resulting from hyperchloremia due to hyporeninemic hypoaldosteronism

Fig. 2

Relationship between albumin, A_TOT, eGFR, and SIG. a Relationship between albumin and A_TOT: A_TOT = 2.6425 × Alb + 2.3323 (R ² = 0.91851). Delta A_TOT is calculated as 11.77 − 2.64 × Alb (g/dL). This number indicates the power to alkalosis. b Relationship between cAG and SIG: SIG = 0.9463 × cAG − 8.1956 (R² = 0.91057). c Relationship between eGFR and SIG: SIG = − 4E-10(eGFR)⁶ + 1E−07(eGFR)⁵ − 1E−05(eGFR)⁴ + 0.0003(eGFR)³ + 0.018(eGFR)² − 1.0314(eGFR) + 19.046 (R² = 0.5943). d Relationship between eGFR and SIG − lactate: (SIG-lactate) = − 5E−10 (eGFR)⁶ + 2E-07 (eGFR)⁵ − 2E−05 (eGFR)⁴ + 0.0008 (eGFR)³ − 4E−05 (eGFR)² − 0.7119 (eGFR) + 15.952 (R ² = 0.6589) (c, d). Six out of 9 patients with eGFR less than 29 mL/min had metabolic acidosis with an increased anion gap. Five out of 6 patients had accumulation of lactate and unknown non-volatile acids (i.e., uremic toxins). One patient had increased levels of lactate alone. On the other hand, increased lactate levels were observed in patients with eGFR greater than 30 mL/min, who have metabolic acidosis and an increased anion gap